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Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice
INTRODUCTION: Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI). Present models of VILI use exceptionally large tidal volumes, causing gross lung injury and haemodynamic shock. In addition, animals are ventilated for a relative short period of time and only after a 'pr...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688111/ https://www.ncbi.nlm.nih.gov/pubmed/19152704 http://dx.doi.org/10.1186/cc7688 |
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author | Wolthuis, Esther K Vlaar, Alexander PJ Choi, Goda Roelofs, Joris JTH Juffermans, Nicole P Schultz, Marcus J |
author_facet | Wolthuis, Esther K Vlaar, Alexander PJ Choi, Goda Roelofs, Joris JTH Juffermans, Nicole P Schultz, Marcus J |
author_sort | Wolthuis, Esther K |
collection | PubMed |
description | INTRODUCTION: Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI). Present models of VILI use exceptionally large tidal volumes, causing gross lung injury and haemodynamic shock. In addition, animals are ventilated for a relative short period of time and only after a 'priming' pulmonary insult. Finally, it is uncertain whether metabolic acidosis, which frequently develops in models of VILI, should be prevented. To study VILI in healthy mice, the authors used a MV model with clinically relevant ventilator settings, avoiding massive damage of lung structures and shock, and preventing metabolic acidosis. METHODS: Healthy C57Bl/6 mice (n = 66) or BALB/c mice (n = 66) were ventilated (tidal volume = 7.5 ml/kg or 15 ml/kg; positive end-expiratory pressure = 2 cmH(2)O; fraction of inspired oxygen = 0.5) for five hours. Normal saline or sodium bicarbonate were used to correct for hypovolaemia. Lung histopathology, lung wet-to-dry ratio, bronchoalveolar lavage fluid protein content, neutrophil influx and levels of proinflammatory cytokines and coagulation factors were measured. RESULTS: Animals remained haemodynamically stable throughout the whole experiment. Lung histopathological changes were minor, although significantly more histopathological changes were found after five hours of MV with a larger tidal volume. Lung histopathological changes were no different between the strains. In both strains and with both ventilator settings, MV caused higher wet-to-dry ratios, higher bronchoalveolar lavage fluid protein levels and more influx of neutrophils, and higher levels of proinflammatory cytokines and coagulation factors. Also, with MV higher systemic levels of cytokines were measured. All parameters were higher with larger tidal volumes. Correcting for metabolic acidosis did not alter endpoints. CONCLUSIONS: MV induces VILI, in the absence of a priming pulmonary insult and even with use of relevant (least injurious) ventilator settings. This model offers opportunities to study the pathophysiological mechanisms behind VILI and the contribution of MV to lung injury in the absence of pre-existing lung injury. |
format | Text |
id | pubmed-2688111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-26881112009-05-30 Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice Wolthuis, Esther K Vlaar, Alexander PJ Choi, Goda Roelofs, Joris JTH Juffermans, Nicole P Schultz, Marcus J Crit Care Research INTRODUCTION: Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI). Present models of VILI use exceptionally large tidal volumes, causing gross lung injury and haemodynamic shock. In addition, animals are ventilated for a relative short period of time and only after a 'priming' pulmonary insult. Finally, it is uncertain whether metabolic acidosis, which frequently develops in models of VILI, should be prevented. To study VILI in healthy mice, the authors used a MV model with clinically relevant ventilator settings, avoiding massive damage of lung structures and shock, and preventing metabolic acidosis. METHODS: Healthy C57Bl/6 mice (n = 66) or BALB/c mice (n = 66) were ventilated (tidal volume = 7.5 ml/kg or 15 ml/kg; positive end-expiratory pressure = 2 cmH(2)O; fraction of inspired oxygen = 0.5) for five hours. Normal saline or sodium bicarbonate were used to correct for hypovolaemia. Lung histopathology, lung wet-to-dry ratio, bronchoalveolar lavage fluid protein content, neutrophil influx and levels of proinflammatory cytokines and coagulation factors were measured. RESULTS: Animals remained haemodynamically stable throughout the whole experiment. Lung histopathological changes were minor, although significantly more histopathological changes were found after five hours of MV with a larger tidal volume. Lung histopathological changes were no different between the strains. In both strains and with both ventilator settings, MV caused higher wet-to-dry ratios, higher bronchoalveolar lavage fluid protein levels and more influx of neutrophils, and higher levels of proinflammatory cytokines and coagulation factors. Also, with MV higher systemic levels of cytokines were measured. All parameters were higher with larger tidal volumes. Correcting for metabolic acidosis did not alter endpoints. CONCLUSIONS: MV induces VILI, in the absence of a priming pulmonary insult and even with use of relevant (least injurious) ventilator settings. This model offers opportunities to study the pathophysiological mechanisms behind VILI and the contribution of MV to lung injury in the absence of pre-existing lung injury. BioMed Central 2009 2009-01-19 /pmc/articles/PMC2688111/ /pubmed/19152704 http://dx.doi.org/10.1186/cc7688 Text en Copyright © 2009 Wolthuis et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Wolthuis, Esther K Vlaar, Alexander PJ Choi, Goda Roelofs, Joris JTH Juffermans, Nicole P Schultz, Marcus J Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice |
title | Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice |
title_full | Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice |
title_fullStr | Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice |
title_full_unstemmed | Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice |
title_short | Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice |
title_sort | mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688111/ https://www.ncbi.nlm.nih.gov/pubmed/19152704 http://dx.doi.org/10.1186/cc7688 |
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